What is being tested?
17-hydroxyprogesterone (17-OHP) is a steroid hormone that is produced as part of the process of making the hormone cortisol. This test measures the amount of 17-OHP in the blood to detect and/or evaluate congenital adrenal hyperplasia (CAH), an inherited condition that results in decreased adrenal cortisol and aldosterone and increased male sex hormone (androgen) production.
17-OHP is derived from cholesterol. It is not an active steroid hormone, but is a precursor that can be converted to active hormones.
The adrenal glands produce the hormone coritsol, which helps break down protein, glucose, and lipids, maintains blood pressure, and regulates the immune system. The adrenal glands also produce other steroid hormones such as aldosterone, which helps regulate salt levels and blood pressure, and androgens, substances that, like testosterone, cause male sexual features as well as other effects.
Several enzymes are required to complete the steps involved in the production of cortisol. If one or more of these enzymes is deficient or dysfunctional, then inadequate amounts of cortisol are produced, as occurs with CAH. The most common cause of CAH is a partial or complete lack of the enzyme 21-hydroxylase, accounting for about 90% of cases.
Because a low level of cortisol causes an elevation in the level of a particular pituitary hormone that stimulates adrenal growth and hormone production (adrenocorticotropic hormone, or ACTH), the adrenal gland increases in size (adrenal hyperplasia). However, the increased size and activity cannot overcome the block in cortisol production. Other substances such as 17-hydroxyprogesterone and androgens that do not need the defective enzyme are produced in excess. This is why testing for 17-OHP can help to detect CAH.
CAH is a group of inherited disorders caused by specific gene mutations and associated with cortisol-related enzyme deficiencies. About 90% of CAH cases are caused by a mutation in the 21-hydroxylase gene (also called CYP-21 or P450c1 or CYP21A2) and may be detected due to the accumulation of 17-OHP in the blood. The disease is caused when both genes, one from each parent, have mutations that decrease or stop the activity of the enzyme for which the gene codes. Parents may be carriers, and carriers may not have any signs of the disease.
CAH with 21-hydroxylase deficiency is inherited as either a severe or mild type:
- Severe forms can cause babies to be born with serious deficiencies of both aldosterone and cortisol that will require medical attention. This severe form is most often detected in infancy during routine newborn screening or during early childhood. If not detected by screening, it may present in early childhood with signs and symptoms such as vomiting, listlessness, lack of energy (lethargy), not eating well, failure to thrive, dehydration and low blood pressure, particularly with acute illness. Due to the excess androgens, the development of male sexual characteristics in females (virilization) can occur. Female babies may have sex organs that are not clearly male or female (ambiguous genitalia), making it difficult to initially determine their sex. Females may have excess hair growth on face and body (hirsutism) and other male secondary sexual characteristics during childhood and adolescence as well as irregular menstruation. Males with this condition will appear normal at birth but may start to develop sexual characteristics prematurely and are at risk for fertility issues later in life.
- In the milder, yet more common form of CAH due to 21-hydroxylase deficiency, there may be only partial deficiency of the enzyme. This type, sometimes called late-onset or non-classical CAH, can have symptoms that begin to appear any time during childhood, adolescence, or adulthood. The symptoms can be vague, may develop slowly over time, and may vary from person to person. Though this form of CAH is not life-threatening, it may cause problems with growth, development, and puberty in children and may lead to infertility in adults.
How is it used?
The 17-hydroxyprogesterone (17-OHP) test is used to screen for congenital adrenal hyperplasia (CAH) and may be used along with other tests to help diagnose and monitor CAH.
- The 17-OHP test is routinely ordered as part of newborn screening in the United States to detect CAH due to 21-hydroxylase deficiency.
- The 17-OHP test may be used to screen for CAH in older children or adults before symptoms appear or to confirm a CAH diagnosis in people with symptoms.
- Measurement of 17-OHP in the blood may be used to aid in the diagnosis of CAH in older children and adults who may have a milder, “late-onset” form.
- If someone is diagnosed with 21-hydroxylase deficiency, a 17-OHP test along with plasma renin activity, androstenedione and testosterone tests may be used periodically to monitor the effectiveness of treatment.
Ruling out CAH
- A 17-OHP test may also sometimes be used, along with other hormone tests, to help rule out CAH in women who have symptoms such as excess facial and body hair and irregular periods. This includes women with suspected polycystic ovarian syndrome (PCOS) and infertility, and rarely those with suspected adrenal or ovarian cancers.
17-OHP testing, especially the newborn screening test, may produce false-positive results. If the level is elevated but not so high that it is diagnostic of CAH, other tests may be performed, such as:
- An ACTH stimulation test may be also be ordered as a follow-up test. In CAH, ACTH stimulation will markedly increase 17-OHP levels.
- Genetic testing may be performed to detect CYP21A2 gene mutations that can cause the condition.
- A karyotype test may be ordered as a follow-up test to detect chromosome disorders and to help determine a baby’s sex.
- Electrolytes may be ordered to measure the person’s sodium and potassium levels.
When is it ordered?
The 17-OHP test is ordered routinely as part of a newborn screen and may be repeated if the screening test is elevated in order to confirm the initial results.
A 17-OHP test may be ordered when an infant or young child has signs and symptoms of adrenal insufficiency or of CAH. Some signs and symptoms may include:
- Listlessness, lack of energy (lethargy)
- Not eating well
- Skin color that looks more tanned than would be otherwise expected
- Low blood pressure
- Sex organs that are not clearly male or female (ambiguous genitalia)
- Development of male secondary sex characteristics (virilization)
This test may sometimes be ordered in older children or in adults when the milder form of CAH (late-onset) is suspected. The 17-OHP test may also be conducted when a girl or woman is experiencing symptoms that may be due to CAH or may be due to another condition, such as PCOS. Symptoms may include:
- Excess facial and body hair (hirsutism)
- Lack of or irregular menstrual periods (menses)
- Development of male secondary sex characteristics
Testing may be performed on boys or men when they experience:
- Early (precocious) puberty
When a person has been diagnosed with 21-hydroxylase deficiency, then a 17-OHP test may be ordered periodically to monitor the effectiveness of treatment.
What does the test result mean?
If a newborn or infant has significantly elevated concentrations of 17-OHP, then it is likely that he or she has CAH. If a person has moderately increased levels, then that person may have a less severe case of CAH or may have an 11-beta-hydroxylase deficiency (another enzyme defect that is associated with CAH).
Normal 17-OHP results mean that it is likely that the person tested does not have CAH due to a 21-hydroxylase deficiency.
Low or decreasing concentrations in a person with CAH indicate a response to treatment. High or increasing levels may indicate that changes in treatment are required.
Is there anything else I should know?
Sometimes an ACTH stimulation is required to increase the diagnostic accuracy of the 17-OHP test. This test involves measuring the level of cortisol in a person’s blood before and after an injection of synthetic ACTH. In CAH, ACTH stimulation will markedly increase 17-OHP levels.
Premature infants often have elevated levels of 17-OHP. The newborn screen may need to be repeated at a later time.
Rarely, prenatal 17-OHP testing may be performed on amniotic fluid to detect and treat CAH in the fetus during pregnancy. Treatment of the fetus before birth is controversial.
Can I have CAH if no CYP21A2 gene mutations were detected during genetic testing?
Yes. Testing detects the most common mutations but will not detect those that are rare. If a specific mutation has been identified in your family members, then you should be tested for that mutation. Also, this test only detects CAH due to 21-hydroxylase deficiency. Other, less common types of CAH will not have mutations in the CYP21A2 gene.
Should I tell all of my healthcare practitioners if I have CAH?
Yes, this is an important thing for all of your health practitioners to know. Most people with CAH will require the regular replacement of one or more hormones and will need to be monitored.
If I have CAH, or my child does, should my family members be tested?
You should talk to your health practitioner or a genetic counselor about this. Since CAH is caused by an autosomal recessive genetic mutation, both parents must have an altered gene in order for a child to have the condition. If both parents are carriers then each child has a 25% chance of having the condition.
How long will it take for 17-hydroxyprogesterone results?
This depends on the laboratory performing the test. 17-OHP testing requires specialized equipment and is not offered by every laboratory. It may be necessary to send your blood sample to a reference laboratory and it may be several days to weeks for results to be available.
How can the healthcare practitioner determine the sex of a baby with sex organs that are not clearly male or female?
Chromosome analysis (karyotyping) can be performed to identify whether the baby has XX (female) or XY (male) sex chromosomes.